Frzb is a secreted protein, initially isolated from purified cartilage extracts, which shares homology to the cysteine rich domain (CRD) of the frizzled family of Wnt receptors. The Wnt proteins are secreted signaling molecules having numerous developmental functions, including skeletal development, as well as dysfunction in oncogenesis. It has been shown that Frzb can bind to and inactivate Wnt activity, leading to speculation for its potential therapeutic use in modifying Wnt induced developmental and oncogenic events. We have demonstrated that Frzb is temporally and spatially expressed during skeletal and craniofacial development. In an attempt to understand the role of Frzb in development we are conducting a conditional gene knockout, using the Cre-LoxP recombination system. We first generated floxed mice, in which the Frzb gene is flanked by LoxP sites, by homologous recombination. These mice were subsequently crossed to a transgenic mouse line expressing Cre recombinase under the control of a ubiquitous promoter to delete Frzb early in development. The null phenotype appears to be lethal and we are currently determining at what stage the lethality occurs. Consequently, in order to observe the effect that loss of Frzb has during face development we are generating a transgenic mouse line to express Cre recombinase specifically in facial mesenchyme. These mice, which express Cre under the control of the Msx-1 promoter, are currently being tested for the specificity of the Cre recombinase activity. - development, wnt receptors, signaling